Supplementary Material for: Effects of Phosphate Binder Therapy on Vascular Stiffness in Early-Stage Chronic Kidney Disease

<b><i>Background/Aims:</i></b> Cardiovascular disease (CVD) is increased in chronic kidney disease (CKD), and contributed to by the CKD-mineral bone disorder (CKD-MBD). CKD-MBD begins in early CKD and its vascular manifestations begin with vascular stiffness proceeding to increased carotid artery intima-media thickness (cIMT) and vascular calcification (VC). Phosphorus is associated with this progression and is considered a CVD risk factor in CKD. We hypothesized that modifying phosphorus balance with lanthanum carbonate (LaCO₃) in early CKD would not produce hypophosphatemia and may affect vascular manifestations of CKD-MBD. <b><i>Methods:</i></b> We randomized 38 subjects with normophosphatemic stage 3 CKD to a fixed dose of LaCO₃ or matching placebo without adjusting dietary phosphorus in a 12-month randomized, double-blind, pilot and feasibility study. The primary outcome was the change in serum phosphorus. Secondary outcomes were changes in measures of phosphate homeostasis and vascular stiffness assessed by carotid-femoral pulse wave velocity (PWV), cIMT and VC over 12 months. <b><i>Results:</i></b> There were no statistically significant differences between LaCO₃ and placebo with respect to the change in serum phosphorus, urinary phosphorus, tubular reabsorption of phosphorus, PWV, cIMT, or VC. Biomarkers of the early CKD-MBD such as plasma fibroblast growth factor-23, Dickkopf-related protein 1 (DKK1), and sclerostin were increased 2- to 3-fold at baseline, but were not affected by LaCO₃. <b><i>Conclusion</i></b>: Twelve months of LaCO₃ had no effect on serum phosphorus and did not alter phosphate homeostasis, PWV, cIMT, VC, or biomarkers of CKD-MBD

Supplementary Material for: Left Ventricular Mass Progression despite Stable Blood Pressure and Kidney Function in Stage 3 Chronic Kidney Disease

<b><i>Background/Aims:</i></b> Progressive chronic kidney disease (CKD) is associated with worsening cardiovascular (CV) risk not explained by traditional risk factors. Left ventricular (LV) hypertrophy (LVH) is an important CV risk factor, but its progression has not been documented in early CKD. We explored whether progression of LVH in early CKD would occur despite stable kidney function. <b><i>Methods:</i></b> We conducted a post hoc analysis of a 12-month study of lanthanum carbonate in stage 3 CKD, which included longitudinal assessments of CV biomarkers. Primary outcome for the analysis was the change in LV mass (LVM) indexed to height in meters^2.7 (LVM/Ht^2.7). Secondary outcomes were changes in blood pressure (BP), pulse-wave velocity, LV systolic/diastolic function, fibroblast growth factor 23 (FGF23), klotho, and estimated glomerular filtration rate (eGFR). <b><i>Results:</i></b> Thirty-one of 38 original subjects had sufficient data for analysis. LVM/Ht^2.7 increased (47 ± 13 vs. 53 ± 13 g/m^2.7, p = 0.006) over 12 months despite stable BP, stable eGFR and normal LV systolic function. Vascular stiffness and LV diastolic dysfunction persisted throughout the study. Klotho levels decreased (748 ± 289 to 536 ± 410 pg/ml, p = 0.03) but were unrelated to changes in LVM/Ht^2.7. The change in FGF23/klotho ratio was strongly correlated with changes in LVM/Ht^2.7 (r² = 0.582, p = 0.03). <b><i>Conclusion:</i></b> Subjects with stage 3 CKD exhibited increasing LVM, persistent LV diastolic dysfunction and vascular stiffness despite stable kidney function, BP and LV systolic function. Abnormal FGF23 signaling due to reduced klotho expression may be associated with increasing LVM. These findings deserve further evaluation in a larger population given the adverse prognostic value of these CV biomarkers